tbuckley/cabot-search huggingface dataset:
P102: Comparison of Novel Salvage Regimens and Traditional salvage Chemotherapy in Relapsed and Refractory Classic Hodgkin Lymphoma
Authors: Harsh Shah, Victoria Vardell, Erin Zacholski, Amanda Fegley, Kalub Fedak, Suchitra Sundaram, Sridevi Rajeeve, Gaurav Goyal, Haris Hatic, Pallawi Torka, Sheeba Ba Aqeel, Azra Borogovac, Kira Macdougall, Shalin Kothari, Anna Kress, Dipenkumar Modi, Elizabeth Travers, Nitin Chilakamarri, Elizabeth Brem, Deborah M. Stephens, Boyu Hu, Lindsey Fitzgerlad, Charlotte Wagner, Daniel Ermann
Journal: HemaSphere (2022)

Table 1: Baseline Characteristics of CT and NT cohortsFigure 1: Comparison of EFS between CT and NT cohorts Background: Novel agents such as brentuximab vedotin (BV) and check-point inhibitors (CPIs) have high response rates in patients with relapsed/refractory (r/r) classical Hodgkin Lymphoma (cHL) and have recently been used as salvage regimens to induce remissions before autologous stem cell transplant (ASCT). Our aim was to compare the outcomes of pts receiving salvage chemotherapy (CT) as opposed to novel treatments (NT) for their first salvage regimen for r/r cHL since limiting data exists regarding their efficacy. Methods: Adult pts with r/r cHL who received their first salvage regimen (SR1) between January 2018 and June 2020 were retrospectively identified. Endpoints were to compare complete response (CR), overall response rate (ORR), and event free survival (EFS) between the CT and NT cohorts. Results: 120 pts were identified with a median age of 33 years (range 18–85). 68% had advanced disease and 13% were early stage unfavorable at diagnosis. Many pts had poor prognostic characteristics including 43% with primary refractory disease, 52% with relapse <12 months from diagnosis, 38% with extranodal disease, and 26% with B-symptoms at time of relapse (Table 1). 65% of pts (n=78) received CT and 35% (n=42) received NT for SR1. 90% of CT pts received Ifosfamide, Carboplatin, and Etoposide (ICE) as SR1. Regimens used for NT treated pts included BV + Bendamustine (43%), BV alone (36%), BV + CPI (12%), BV + CT (5%), and other CPI (4%). No significant difference was found in the ORR and CR rates according to pts treated with CT vs. NT of 67% vs. 69% and 47% vs. 55%, respectively. 88% of those who received CT for SR1 and 83% of those who received NT for SR1, eventually had ASCT. At a median follow-up of 32 months, 1-year EFS was 57% vs 69% and 2-year EFS was 56% vs 66% between CT and NT cohorts (p=0.25) (Figure 1). All pts who progressed after CT for SR1 (n=31) received NT for SR2; whereas 73% (n=11) of those progressing after NT for SR1 received CT for SR2. ORR for CT in SR2 was 91% vs 70% for NT (p=.48). 79% vs 89% remained progression-free post-ASCT at their last follow-up after receiving CT vs. NT at last salvage before ASCT respectively (p=0.15). Conclusion: There was a numerical trend towards better CR and EFS for novel therapy compared to traditional chemotherapy for first salvage, however the outcomes were not statistically significant, demonstrating that chemotherapy is still a valid option for salvage before ASCT.
P094: Long-term outcomes of bulky classic Hodgkin lymphoma managed with a PET-adapted approach demonstrate excellent outcomes in PET-negative cases
Authors: Jowon Laura Kim, Diego Villa, R. Petter Tonseth, Alina S. Gerrie, Don Wilson, Francois Benard, Chris Venner, Brian Skinnider, Pedro Farinha, Graham W. Slack, David W. Scott, Joseph M. Connors, Laurie H. Sehn, Kerry J. Savage
Journal: HemaSphere (2022)

Figure 1: Freedom from treatment failure in bulky advanced stage cHL pts by post-ABVD chemotherapy PET scan (A) and Deauville score (B). Overall survival in bulky advanced stage cHL pts by post-ABVD chemotherapy PET scan (C) and Deauville score (D). Background: With concerns of long-term complications due to radiotherapy (RT), recent studies have evaluated ABVD alone in patients (pts) with bulky classic Hodgkin lymphoma (cHL) with an end of treatment (EOT) PET-negative (neg) scan. However, variable definitions of bulky disease are used, and long-term follow-up remains limited. Since 2005, advanced stage (stage 2B/3/4, bulky (≥10cm) stage 1/2) cHL pts in British Columbia (BC) have been managed with PET-guided consolidative RT. Methods: The BC Cancer Lymphoid Cancer Database was screened to identify all pts >16 years (y) with bulky (≥10cm) cHL treated with 6 cycles of ABVD chemotherapy. Pts with progressive disease on interim scan or at EOT were excluded. Pts with an EOT PET-positive (pos) scan received consolidative RT. PET scans assessed by the IHP criteria were re-reviewed to assign a Deauville (D) score (PET-neg=D1-3, DX; PET-pos=D4-5). Freedom from treatment failure (FFTF) was measured from diagnosis to relapse/ progression of HL, or death due to HL or treatment toxicity. Results: From 2005–2020, 215 patients (115M, 100F) were identified. Median age was 29 years (y) (17-72y), median mass size was 11cm (10-21cm), 94% had bulky mediastinal mass, and 2%, 65%, 8%, and 25% had stage 1, 2, 3 and 4 disease, respectively. At EOT, 176 (82%) had a PET-neg scan (none received RT), and 39 (18%) had a PET-pos scan (34 received RT to residual mass; 5 were observed: false pos n=3, refused n=1, not radioencompassable n=1). With a median follow-up of 6.75y (0.8–15.75y), pts with a PET-neg scan had 5y FFTF of 94% (stage 1/2–94%, stage 3/4–96%) vs 65% with a PET-pos scan (p<0.001). Overall survival (OS) was similar in PET-neg and pos (97% vs 90%, p=0.191). The 5y FFTF was similar by D score in PET-neg cases (DX-100%; D1-90.5%; D2-97%; D3-100%, p=0.213) but inferior in D4 (58%) and D5 (42%) (p<0.001). The 5y OS was similar between PET-neg and D4 (DX-93%, D1-97%, D2-100%, D3-100%, D4-94%), but inferior in D5 cases, with 5y OS 60% (p=0.015). There were 23 relapses: 10 PET-neg (7 in what would have been the RT field (residual mass), 3 inside and outside field); 13 PET-pos (5 in field, 8 included sites outside the RT field). Conclusion: With a median follow-up of almost 7y, bulky cHL with an EOT PET-neg scan have excellent outcomes, regardless of initial stage. A large proportion of D4 PET-pos cases are salvaged with RT and maintain an excellent OS. Both FFTF and OS are inferior in those with an EOT D5 scan.
P032: Circulating immune biomarkers in classical Hodgkin lymphoma in relation to tumor burden and response to treatment.
Authors: Tom A. Mulder, Maria L. Andersson, Lucia Peña-Pérez, Kia Heimersson, Ioanna Xagoraris, Björn E. Wahlin, Robert Månsson, Lotta Hansson, Georgios Z. Rassidakis, Marzia Palma
Journal: HemaSphere (2022)

Background: In classical Hodgkin lymphoma (cHL) the malignant cells represent only a small fraction of the tumor mass. Yet, they orchestrate a lymphocyte-dominated tumor microenvironment (TME) that supports their survival and growth. The systemic effects of this local immunomodulation are not fully elucidated. In this study, we aimed at characterising circulating lymphocytes and plasma proteins in cHL patients in relation to clinical parameters and treatment effect. Methods: Peripheral blood (PB) samples were obtained from 48 consecutive patients at diagnosis (baseline, BL) and at 2 time points after primary treatment, right at the end of treatment (EoT) and at follow-up 6 months after EoT (FU). Twenty-eight patients had limited-stage (I-IIA) and 20 had advanced-stage (IIB-IV) disease. All the patients in the FU analysis were in complete remission. Twenty healthy individuals were included as controls. Cells from PB and LN were freshly analysed by flow cytometry, and plasma proteins by proximity extension assay (PEA). Concentrations of CCL17/TARC in plasma were also measured by Enzyme-Linked ImmunoSorbent Assay. Results: At BL, the numbers of B cells were lower in both limited- and advanced-stage cHL compared to controls, while T cells were normal. Advanced-stage patients had fewer NK cells with a functionally impaired phenotype. Compared to controls, cHL patients had higher frequencies of proliferating T cells as well as higher expression of programmed death (PD)-1 and cytotoxic T lymphocyte antigen (CTLA)-4 in circulating T cells, and lower naïve T-cell frequencies. The plasma concentration of CCL17/TARC was elevated in both limited- and advanced-stage cHL compared to controls. The frequencies of T and B cells positively correlated between the PB and LN compartments. Distinct immune cellular and plasma protein biomarker profiles were observed in patients with a high tumor burden (i.e. bulky tumor and/or >2 nodal sites involved and/or stage IV) and those with high inflammation (i.e. ESR ≥50). T-cell exhaustion and NK-cell depletion were reversed by standard first-line treatment and CCL17/TARC concentrations also dropped back to control levels. Patients who received radiotherapy involving the mediastinum had low T-cell counts for a prolonged period. Conclusion: The immunomodulation of lymphocytes in the TME of cHL might affect immune biomarkers in the PB. Most immunological changes are reverted after successful standard primary treatment.
T087: Brentuximab vedotin (Bv) Demonstrates Superior Event-Free Survival in Pediatric High-Risk Hodgkin Lymphoma
Authors: Sharon M. Castellino, Qinglin Pei, Susan K. Parsons, David Hodgson, Kathleen Mccarten, Terzah Horton, Steve Cho, Yue Wu, Angela Punnett, Hema Dave, Tara O. Henderson, Bradford S. Hoppe, Ann-Marie Charpentier, Frank G. Keller, Kara M. Kelly
Journal: HemaSphere (2022)

Figure 1: Event Free Survival (EFS) by study arm: The hazard for events of progression, death or second malignant neoplasm (SMN) was 0.41 (95% CI 0.25, 0.67), in favor of Bv-AVE-PC. No. of first events: Bv-AVE-PC, n=23; ABVE-PC, n=51 Background: The use of the anti-CD30 antibody drug conjugate, Brentuximab vedotin (Bv) has not been established as first line therapy for Hodgkin lymphoma (HL) in children or adolescents. We compared the efficacy and safety of Bv with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (Bv-AVE-PC) to the standard pediatric dose intensive regimen ABVE-PC, inclusive of bleomycin. Methods: This multicenter randomized, open-label phase 3 study enrolled patients 2–21 years (yrs) with previously untreated HL, stages IIB + bulk, IIIB, IVA, IVB (NCT02166463). Patients were randomized to 5 cycles of either ABVE-PC or Bv-AVE-PC given every 21 days with granulocyte colony-stimulating factor support. Centrally reviewed PET-CT after 2 cycles (iPET) defined slow responding lesions (SRL) by 5-point score (PS) >3. Involved site radiotherapy (ISRT) was given to bulky mediastinal adenopathy and SRL. The primary objective was EFS. Results: 600 participants were enrolled across 153 Children’s Oncology Group institutions from March 2015 to August 2019; 587 were eligible. Median age was 15.6 yrs (range 3.4–22). Patient and disease characteristics were balanced across study arms. Stage distribution: 20.6% IIB-bulk; 19.3% IIIB; 28.5% IVA; 31.7% IVB. At a median follow-up of 42.1 mos (0.1–80.9), 3-year EFS (95%CI) by intent-to-treat analyses was 92.1% (88.4, 94.7) with Bv-AVE-PC vs. 82.5% (77.4, 86.5) with ABVE-PC (HR 0.41 (0.25, 0.67), p=0.0002). Cumulative incidence of relapse was 7% with Bv-AVE-PC and 17% following ABVE-PC. iPET+ rates were comparable (ABVE-PC 19% vs. Bv-AVE-PC 18%, p=0.8), but iPET+ patients who received Bv-AVE-PC had a significantly higher 3yr-EFS (90.7%) compared to ABVE-PC (68.3%) (HR 0.28 [0.10, 0.76]). As-treated ISRT receipt did not differ (ABVE-PC 55.7% vs. Bv-AVE-PC 52.7%, p=0.69). No difference was noted in grade 3/4 adverse events; myelosuppression, reflected in a 32% incidence of > grade 3 febrile neutropenia, did not differ by arm (p=0.67). Only 19% of patients experienced > grade 2 neuropathy by the Balis pediatric neuropathy scale, with no difference between arms (p=0.86). Conclusion: Bv with AVE-PC in a dose intensive regimen has superior efficacy to ABVE-PC for pediatric patients with high-risk HL. A 9.6% improvement in EFS was achieved with no increase in toxicity and with fewer patients receiving RT compared to prior pediatric trials for high-risk HL.
P086: Advancing Pediatric Hodgkin Lymphoma Research Through NODAL
Authors: Jamie E. Flerlage, Suzi Birz, Sharon M. Castellino, Burton Appel, Brian Furner, Luca Graglia, Tara O. Henderson, David Hodgson, Bradford S. Hoppe, Justine Kahn, Frank G. Keller, Sandy Kessel, Chen Li, Mei Li, John Lucas, Kathleen Mccarten, Monika Metzger, Sarah Milgrom, Susan K. Parsons, Qinglin Pei, Yue Wu, Yiwang Zhou, Michael Watkins, Sam Volchenbaum, Kara M. Kelly
Journal: HemaSphere (2022)

Background: The Pediatric Cancer Data Commons (PCDC; University of Chicago, established in 2015) has provided a robust technical infrastructure to enable harmonization and utilization of big data to answer meaningful research questions for rare diseases. Access to data is challenging and the PCDC is moving the field forward through rapid access to big data without loss of governance for each individual contributor. The HodgkiN lymphOma DatA coLlaboration (NODAL) is the next step in a longstanding collaboration between pediatric Hodgkin lymphoma (HL) consortia to help advance the field. Methods: Our NODAL subgroup of the PCDC began in 2018 and built on the existing international working group SEARCH for CAYAHL (Staging Evaluation and Response Criteria Harmonization for Childhood, Adolescent and Young Adult HL). The initial collaboration includes an agreement for submission of clinical trial data from COG and St. Jude-Stanford-Dana-Farber clinical trials for classic and lymphocyte predominant HL. During 2019 to 2020 NODAL members worked to harmonize case report forms from clinical trials and develop a comprehensive data dictionary. Foundational steps were made to establish an executive committee, governance structure with policies and procedures, sign a memorandum of understanding to establish the consortium, and data contributor agreements. The NODAL leadership identified research questions for which exploration would be possible with a larger data set than is currently available at any one research group. We used that information to identify working groups that would be ready to start once the data are harmonized. Data are currently being entered into NODAL and next steps will involve utilization of data of nodular lymphocyte predominant Hodgkin lymphoma patients to enable research of this rare subtype of HL previously treated on many classical HL trials. Conclusion: NODAL is a rich resource and will provide access to large datasets from pediatric HL trials that will facilitate cross-trial comparisons and answer unmet clinical research questions in an expeditious manner. We look forward to inclusion of additional international cooperative groups and sharing this rich resource with the global community for years to come.
P034: Correlation between MTV, TLG and Serum TARC Concentration in Classical Hodgkin Lymphoma during First-Line Treatment
Authors: Ilaria Romano, Benedetta Puccini, Elisabetta Abenavoli, Leonardo Signori, Marianna Palazzo, Manuel Ciceri, Benedetta Sordi, Valentina Berti, Michela Zizza, Fabiana Pancani, Luca Nassi, Alessandro Maria Vannucchi
Journal: HemaSphere (2022)

Table 1: Median LogRED for PET-variables and sTARC Table 2: Median LogΔ for PET-variables and sTARC Introduction: Positron emission tomography (PET) is an available tool to adapt treatment strategy in newly diagnosed classical Hodgkin Lymphoma (HL). However, approximately 15% of patients (pts) with negative interim PET (iPET) still experience relapse. Here, we aimed at correlating PET-variables, namely metabolic tumor volume (MTV) and total lesion glycolysis (TLG), with serum TARC (sTARC), a promising predictor of response in HL. Methods: We prospectively collected plasma samples of 58 untreated HL pts, stratified according to GHSG risk categories and treated according to a PET-driven strategy. Samples were collected at baseline, after 2 cycles of ABVD (coinciding with iPET), and at the end of treatment (EOT). All pts underwent PET scan at the same timepoints. Thresholds used for measuring MTV and TLG were SUVmax>2.5 and 41% of the SUVmax. Deauville ≤3 defines complete remission. To assess interim response, variables were evaluated as logarithmic reduction (LogRED) of baseline vs iPET, and as logarithmic variation (LogΔ) of EOT vs iPET for EOT response. Results: Overall, 45 out of 58 pts were evaluable. We excluded 12 pts due to unavailable PET scan at any timepoint, and 1 for missing samples. Median age was 33 years (17–58), 60% pts were male, 58% pts had B-symptoms and 71% were diagnosed with an advanced stage (IIB, III, IV). Five (11%) pts were iPET+ and 5 (11%) were EOT-PET+. Results of LogRED and LogΔ for TLG 2.5, TLG 41%, MTV 2.5, MTV 41% and sTARC in both iPET- and iPET+ pts are listed in Table 1 and Table 2, respectively. Overall, LogRED of PET variables were significantly lower in iPET+ compered to iPET- pts (p<.001), while no differences were observed for LogRED of sTARC (p=.4). In EOT+ pts, the LogΔ for both PET-variables and sTARC was significantly different (p<.001). The correlation between PET variables and sTARC showed a significant trend for LogRED using the 2.5 threshold for MTV and TLG (respectively, r=.333, p=.026 and r=.304, p=.042), but not for the 41% cut-off (r=.298, p=.052 and r=.268, p=.083). LogΔ between PET-variables vs sTARC were significantly correlated (r=.427, p=.004 for TLG 2.5, r=.404, p=.007 for TLG 41%, r=.427, p=.004 for MTV 2.5 and r=.401, p=.008 for MTV 41%). Conclusion: Our findings show that the PET scan and sTARC are intercorrelated predictors in HL, with the latter potentially being a helpful marker for identifying iPET-/EOT-PET+ pts. Larger studies are needed to confirm the role of sTARC monitoring.
P078: Predicting the Health-Related Quality of Life of Hodgkin Lymphoma Survivors: Identification of Risk Factors
Authors: Nele Stadtbaeumer, Axel Mayer, Peter Borchmann
Journal: HemaSphere (2022)

Introduction: Cancer survivors are at risk of long-term impairment of their health-related quality of life (HRQoL), persisting for years after treatment. Despite the clinical importance, research is scarce and the etiology is complex. The aim of this study is to develop prediction models for different HRQoL domains of Hodgkin Lymphoma (HL) survivors. Therefore, we identify risk factors at the time of cancer diagnosis, as well as during and after therapy. Methods: Data of N=4981 patients from diagnosis to year five of survival of the fifth study generation (HD13-15) of the German Hodgkin Study Group was analyzed. Parametric (forward stepwise regression, lasso, and all-pairs lasso) and non-parametric (bagged and boosted regression trees) machine learning algorithms were investigated to identify the relevant risk factors out of a set of 61 potential demographic, physical and psychosocial predictors. HRQoL was measured with the EORTC QLQ-C30. Assessed HRQoL domains were overall HRQoL, cancer-related fatigue, employment, and financial status, and physical, emotional, cognitive, social, and role functioning. Results: The all-pairs lasso algorithm performed best at detecting the relevant predictors in comparison to the other methods tested. All-pairs lasso identified between six and 17 risk factors for each HRQoL domain. The risk factors included patients’ age, prior HRQoL levels, specific physical risk factors, and the cancer stage. Based on the variable selection we estimated regression models to predict each HRQoL domain. Cross-validation showed that each baseline prediction model explained around 30%–33% of the variability of the corresponding outcome. Conclusions: Our analysis reveals relevant risk factors of each HRQoL domain in HL survivors. The complex interplay between several demographic, physical and psychosocial predictors has some predictive power for the HRQoL levels after therapy. The possibility of predicting HRQoL at the time of diagnosis and during and after therapy contributes to a better understanding of HRQoL in HL survivors and informs the development of much-needed interventions.
P054: The Kinase CK2 is deregulated and targetable in classical Hodgkin Lymphoma
Authors: Andrea Visentin, Edoardo Ruggeri, Federica Frezzato, Marco Pizzi, Alessandro Cellini, Francesco Angotzi, Chiara Adele Cavarretta, Valeria Ruocco, Stefano Pravato, Filippo Severin, Monica Facco, Sabrina Manni, Francesci Piazza, Livio Trentin
Journal: HemaSphere (2022)

Introduction: CK2 is a pleiotropic kinase consisting of 2 catalytic (a) and 2 regulatory (b) subunits, usually overexpressed, that sustains cancer signaling cascades through the activation of NF-kB, PI3K and STAT pathways. Considering that NF-kB, STAT and PI3K pathways are key players in Hodgkin lymphoma (HL), it is likely that CK2 might play a role in the pathogenesis of this disease. Methods: Experiments were performed and replicated at least for five times employing 4 HL cell lines (L-428, L-540, KM-H2 and HDLM-1) cultured in RPMI. CK2a, CK2b, RelA-Serine (S)529, RelA, PARP, AKT-S473, AKT, STAT3-S727, STAT3, tubulin, ubiquitin expression levels were evaluated by western blot analysis (WB). Silmitasertib and bortezomib were used as CK2a and proteasome inhibitors. Apoptosis was assessed by Annexin V/Propidium iodide assay and PARP cleavage by WB. Immunohistochemistry (IHC) for CK2a and CK2b was performed on formalin fixed paraffin embedded sections of lymph-nodes from patients with HL, indolent and aggressive NHL. Chou-Talalay methods was used to calculate the combination index (C.I.) of two drugs. Results: By WB and IF we found that all the 4 HL cell lines expressed higher levels of CK2a, but not CK2b, as compared to normal B lymphocytes (p<0.001). By IHC on 35 patients’ lymph-nodes, we confirmed that CK2a but not CK2b was highly expressed in Reed-Sternberg cells. In addition, patients with lower levels of CK2b display a better progression-free survival (p<0.05). The unbalance between a and b subunits was not observed in low or high-grade NHL (p<0.001). Furthermore, we observed that mRNA levels of both CSNK2A and CSNK2B were similar to normal B lymphocytes, and that proteasome inhibition with bortezomib caused the upregulation of CK2b. AKT, RelA and STAT3 were constitutively phosphorylated in HL at their activatory S-residue (S473, S529, and S727 respectively). Treatment of HL cell lines with silmitasertib caused down-regulation of these phospho-serine proteins, time and dose-dependent apoptosis (p<0.0001). In addition, we found that silmitasertib did not modulate surface CD30 and had a synergistic anti-apoptotic effect in combination with monomethyl auristatin E (C.I.<1) Conclusions: We demonstrated that CK2a is overexpressed, active, induced key pro-survival signals in HL, and its inhibition trigger apoptosis. CK2b is likely downregulated due to proteasome degradation. These preliminary data suggest that CK2 might be a new therapeutic target in HL.